Prenatal NAP plus SAL prevents developmental delay in a mouse model of Down syndrome through effects on N-methyl-D-aspartic acid and γ-aminobutyric acid receptors

OBJECTIVE: Down syndrome (DS) affects 1/800 infants. Prenatal NAPVSIPQ (NAP) and SALLRSIPA (SAL) (NAP + SAL) prevent developmental delay in Ts65Dn mice, a mouse model of DS. We investigated whether this finding involves N-methyl-D-aspartic acid and gamma-aminobutyric acid (GABA) receptor subunits. STUDY DESIGN: Pregnant Ts65Dn mice were treated with placebo or NAP + SAL on gestational days 8-12. After developmental delay prevention was shown, 4 trisomic (Ts), 4 control, and 3 Ts + NAP + SAL adult offspring brains (from 3 litters) were collected. Calibrator-normalized real-time polymerase chain reaction was performed using primers for N-methyl-D-aspartic acid subunits NR2A and NR2B, and for GABA subunits GABA(A)alpha 5 and GABA(A)beta 3 with glyceraldehyde-3-phosphate dehydrogenase stan-dardization. Statistics included analysis of variance and Fisher PLSD with P < .05 as significant. RESULTS: NR2A, NR2B, and GABA(A)beta 3 levels were decreased in Ts vs control (all P < .05). Prenatal NAP + SAL increased NR2A, NR2B, and GABA(A)beta 3 to levels similar to control (all P < .05). A significant difference in GABA(A)alpha 5 levels was not found. CONCLUSION: Prenatal NAP + SAL increases NR2A, NR2B, and GABA(A)beta 3 expression in adult DS mice to levels similar to controls. This may explain how NAP + SAL improve developmental milestone achievement.